Serotonin (5-HT) release and uptake measured by real-time electrochemical techniques in the rat ileum.
Serotonin (5-HT) is released from the enterochromaffin cells and plays an important role in regulating intestinal function. Although the release of 5-HT is well documented, the contribution of the serotonin reuptake transporter (SERT) to the levels and actions of 5-HT in the intestine is unclear. This study aimed to demonstrate real-time SERT activity in ileal mucosa and to assess the effects of SERT inhibition using fluoxetine. Electrochemical recordings were made from the mucosa in full-thickness preparations of rat ileum using a carbon fiber electrode to measure 5-HT oxidation current and a force transducer to record circular muscle (CM) tension. Compression of the mucosa stimulated a peak 5-HT release of 12 +/- 6 microM, which decayed to 7 +/- 4 microM. Blockade of SERT with fluoxetine (1 microM) increased the peak compression-evoked release to 19 +/- 9 microM, and the background levels of 5-HT increased to 11 +/- 7 microM (P < 0.05, n = 7). When 5-HT was exogenously applied to the mucosa, fluoxetine caused a significant increase in the time to 50% and 80% decay of the oxidation current. Fluoxetine also increased the spontaneous CM motility (P < 0.05; n = 7) but did not increase the CM contraction-evoked 5-HT release (P > 0.05, n = 5). In conclusion, this is the first characterization of the real-time uptake of 5-HT into the rat intestine. These data suggest that SERT plays an important role in the modulation of 5-HT concentrations that reach intestinal 5-HT receptors.
Bertrand
Paul P
PP
Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. dr.p.bertrand@gmail.com
Hu
Xiaoya
X
Mach
John
J
Bertrand
Rebecca L
RL
D000818:Animals; D002244:Carbon; D000077482:Carbon Fiber; D004563:Electrochemistry / Q000379:methods*; D004566:Electrodes; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D010208:Papaverine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D002244:Carbon; D000077482:Carbon Fiber; D005473:Fluoxetine; D010208:Papaverine; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493232:Slc6a4 protein, rat